Asthma treatment response modified by fine particulate matter, nitrogen dioxide, and ozone among Black children: A reanalysis of the AsthmaNet Best African American Response to Asthma Drugs trial - 06/05/25

Doi : 10.1016/j.jaci.2025.04.009

Lizbeth F. Gómez, PhD MPH ^a,^⁎ , Ellen J. Kinnee, MS ^b, Michael T. Young, PhD ^c, Joel D. Kaufman, MD, MPH ^c, Anne M. Fitzpatrick, PhD, MSCR, APRN ^d, Sharmilee M. Nyenhuis, MD, FAAAAI ^e, Julian Solway, MD ^f, Steven R. White, MD ^f, Edward T. Naureckas, MD ^f, Wanda Phipatanakul, MD, MS ^g, Michael E. Wechsler, MD, MMSc ^h, Susan J. Kunselman, MS ⁱ, David T. Mauger, MS, PhD ⁱ, Leslie A. McClure, MS, PhD ^j, Usama Bilal, MD, MPH, PhD ^k, Stephen C. Lazarus, MD, FCCP, FERS ^l, Fernando Holguin, MD, MPH ^m, Jane E. Clougherty, MSc, ScD ^a
^a Department of Environmental and Occupational Health, Drexel University Dornsife School of Public Health, Philadelphia, Pa
^b University Center for Social and Urban Research, University of Pittsburgh, Pittsburgh, Pa
^c Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Wash
^d Department of Pediatrics, Emory University, Atlanta, Ga
^e Department of Pediatrics-Allergy and Immunology, University of Chicago, Chicago, Ill
^f Department of Medicine, Pulmonary and Critical Care, University of Chicago, Chicago, Ill
^g Division of Immunology, Boston Children’s Hospital, Boston, Mass
^h Department of Medicine, National Jewish Health, Denver, Colo
ⁱ Department of Public Health Sciences, Pennsylvania State University, University Park, Pa
^j College of Public Health and Social Justice, Saint Louis University, St Louis, Mo
^k Department of Epidemiology and Urban Health Collaborative, Drexel University Dornsife School of Public Health, Philadelphia, Pa
^l Division of Pulmonary & Critical Care Medicine, University of California San Francisco, San Francisco, Calif
^m Medicine-Pulmonary Sciences & Critical Care, University of Colorado School of Medicine, Aurora, Colo

^∗Corresponding author: Lizbeth F. Gómez, PhD, MPH, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.Department of BiostatisticsEpidemiology and InformaticsPerelman School of MedicineUniversity of PennsylvaniaBlockley Hall423 Guardian DrivePhiladelphiaPA19104

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Graphical abstract

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Abstract

Background

Asthma morbidity significantly affects children of all racial backgrounds; however, Black children experience a greater disease burden than children from other racial groups. Despite the known influence of air pollution on asthma outcomes, its role in the efficacy of asthma treatments remains underexplored.

Objective

We sought to examine how exposure to particulate matter <2.5 μm (PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃) influenced treatment outcomes in the National Institutes of Health AsthmaNet Best African American Response to Asthma Drugs trial.

Methods

The trial randomized 224 Black children to 4 asthma treatments consisting of an inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) administered in a randomized crossover fashion. Treatment efficacy was assessed by the frequency of asthma exacerbations, percent predicted FEV₁, and annualized asthma control days. Residential exposures to PM_2.5, NO₂, and O₃ were estimated using a validated spatiotemporal model. Mixed-effects models were used to evaluate the interaction between pollution exposure and treatment efficacy, adjusting for age, household triggers, and trial site.

Results

PM_2.5, NO₂, and O₃ exposures ranged substantially across participants from 2.28 to 15.3 μg/m³, 2.34 to 63.7 ppm, and 2.57 to 23.7 ppb, respectively. NO₂ and PM_2.5 exposures were not associated with increased exacerbations post-treatment (P for interaction = .15 and .08, respectively). However, NO₂ exposure significantly modified the effect of high-dose ICS+LABA therapy on lung function. Children with below median NO₂ exposures while receiving ICS+LABA therapy had a reduction of 5.86 (95% CI 1.16, 10.56) in percent predicted FEV₁ compared with children with above median NO₂ exposures.

Conclusion

Residential high NO₂ exposure may significantly attenuate the efficacy of ICS+LABA therapy on lung function in Black children. These findings suggest the need to consider environmental factors in clinical trials and asthma management strategies.

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Key words : Asthma, ICS, LABA, environmental health, air pollution, randomized clinical trial

Abbreviations used : AACD, BARD, GLI, ICS, LABA, NHLBI, NIH, NO₂, O₃, %PFEV₁, PM_2.5